For example, in the pharmaceutical industry, preparative separation/purification systems utilizing liquid chromatographs are used to collect samples of a variety of chemically synthesized compounds in order to store those samples in a library or analyze them in more detail. Conventional examples of the preparative separation/purification system are disclosed in Patent Documents 1 and 2.
In these conventional apparatuses, target components (compounds) in a sample solution are temporally separated by a liquid chromatograph. The separated target components are then respectively introduced into different trap columns and temporarily captured therein. Subsequently, a solvent is supplied into each trap column to quickly elute the component from the trap column and collect it in a container. Thus, a plurality of solutions each containing one target component at a high concentration are respectively collected in a plurality of containers. These separately collected solutions are then subjected to a vaporizing and drying process to remove the solvent and collect the target components in solid forms.
To improve the collection rate of the target component in this type of preparative separation/purification system, it is necessary to assuredly capture the target compound by the trap column. For this purpose, it is desirable to maximally decrease the elution capability of the solvent (mobile phase) used for introducing a solution containing the target component into the trap column. For example, in the case of a trap column that works in a reverse-phase mode, the adsorbent contained in the trap column is hydrophobic, while the mobile phase is hydrophilic. In this case, using a more hydrophilic mobile phase will make the target compound more strongly held on the adsorbent. Accordingly, some systems dilute the mobile phase with water to lower its elution capability by mixing water, supplied by a separate pump, into the mobile phase at a point before the inlet of the trap column when an eluate containing a target compound separated by a column of a preparative liquid chromatograph is introduced into the trap column.
However, lowering the elution capability of the mobile phase in this manner decreases not only the solubility of the target compound in the mobile phase but also that of foreign compounds. As a result, the target and foreign compounds both easily precipitate within a pipe or trap column, causing clogging or similar problems and thereby impeding the flow of the solutions.
Furthermore, even if a diluting liquid, such as water, is mixed into the mobile phase, the adsorbent in the trap column cannot exhibit an adequate retaining power for some kinds of compounds but allows those compounds to pass through the trap column. This not only results in a failure of the preparative separation but may also cause a loss of the synthesized pharmacological compound. Naturally, it is possible to improve the efficiency of capturing the compound with the trap column by appropriately setting the trapping conditions, such as the kind of adsorbent to be filled into the trap column, the kind of mobile phase or the liquid-supply velocity. However, in the pharmaceutical industry, the preparative separation/purification needs to be performed on such a wide variety of compounds that it requires an extreme amount of time, labor and cost to determine optimal conditions for each and every compound. Therefore, a more versatile preparative separation/preparation method that does not require changing the trapping conditions for a variety of compounds has been requested. However, none of the conventional systems could meet with this requirement.
Patent Document 1: Japanese Unexamined Patent Application Publication No. H02-122260
Patent Document 2: Japanese Unexamined Patent Application Publication No. 2003-149217